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Lung metastases share common immune features regardless of primary tumor origin

BACKGROUND: Only certain disseminated cells are able to grow in secondary organs to create a metastatic tumor. Under the hypothesis that the immune microenvironment of the host tissue may play an important role in this process, we have categorized metastatic samples based on their immune features. M...

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Autores principales: García-Mulero, Sandra, Alonso, M Henar, Pardo, Julián, Santos, Cristina, Sanjuan, Xavier, Salazar, Ramón, Moreno, Victor, Piulats, Josep María, Sanz-Pamplona, Rebeca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319789/
https://www.ncbi.nlm.nih.gov/pubmed/32591432
http://dx.doi.org/10.1136/jitc-2019-000491
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author García-Mulero, Sandra
Alonso, M Henar
Pardo, Julián
Santos, Cristina
Sanjuan, Xavier
Salazar, Ramón
Moreno, Victor
Piulats, Josep María
Sanz-Pamplona, Rebeca
author_facet García-Mulero, Sandra
Alonso, M Henar
Pardo, Julián
Santos, Cristina
Sanjuan, Xavier
Salazar, Ramón
Moreno, Victor
Piulats, Josep María
Sanz-Pamplona, Rebeca
author_sort García-Mulero, Sandra
collection PubMed
description BACKGROUND: Only certain disseminated cells are able to grow in secondary organs to create a metastatic tumor. Under the hypothesis that the immune microenvironment of the host tissue may play an important role in this process, we have categorized metastatic samples based on their immune features. METHODS: Gene expression data of metastatic samples (n=374) from four secondary sites (brain, bone, liver and lung) were used to characterize samples based on their immune and stromal infiltration using gene signatures and cell quantification tools. A clustering analysis was done that separated metastatic samples into three different immune categories: high, medium and low. RESULTS: Significant differences were found between the immune profiles of samples metastasizing in distinct organs. Metastases in lung showed a higher immunogenic score than metastases in brain, liver or bone, regardless of their primary site of origin. Also, they preferentially clustered in the high immune group. Samples in this cluster exhibited a clear inflammatory phenotype, higher levels of immune infiltrate, overexpression of programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) pathways and upregulation of genes predicting clinical response to programmed cell death protein 1 (PD-1) blockade (T-cell inflammatory signature). A decision tree algorithm was used to select CD74 as a biomarker that identify samples belonging to this high-immune subtype of metastases, having specificity of 0.96 and sensitivity of 1. CONCLUSIONS: We have found a group of lung-enriched metastases showing an inflammatory phenotype susceptible to be treated with immunotherapy.
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spelling pubmed-73197892020-07-01 Lung metastases share common immune features regardless of primary tumor origin García-Mulero, Sandra Alonso, M Henar Pardo, Julián Santos, Cristina Sanjuan, Xavier Salazar, Ramón Moreno, Victor Piulats, Josep María Sanz-Pamplona, Rebeca J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: Only certain disseminated cells are able to grow in secondary organs to create a metastatic tumor. Under the hypothesis that the immune microenvironment of the host tissue may play an important role in this process, we have categorized metastatic samples based on their immune features. METHODS: Gene expression data of metastatic samples (n=374) from four secondary sites (brain, bone, liver and lung) were used to characterize samples based on their immune and stromal infiltration using gene signatures and cell quantification tools. A clustering analysis was done that separated metastatic samples into three different immune categories: high, medium and low. RESULTS: Significant differences were found between the immune profiles of samples metastasizing in distinct organs. Metastases in lung showed a higher immunogenic score than metastases in brain, liver or bone, regardless of their primary site of origin. Also, they preferentially clustered in the high immune group. Samples in this cluster exhibited a clear inflammatory phenotype, higher levels of immune infiltrate, overexpression of programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) pathways and upregulation of genes predicting clinical response to programmed cell death protein 1 (PD-1) blockade (T-cell inflammatory signature). A decision tree algorithm was used to select CD74 as a biomarker that identify samples belonging to this high-immune subtype of metastases, having specificity of 0.96 and sensitivity of 1. CONCLUSIONS: We have found a group of lung-enriched metastases showing an inflammatory phenotype susceptible to be treated with immunotherapy. BMJ Publishing Group 2020-06-25 /pmc/articles/PMC7319789/ /pubmed/32591432 http://dx.doi.org/10.1136/jitc-2019-000491 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Clinical/Translational Cancer Immunotherapy
García-Mulero, Sandra
Alonso, M Henar
Pardo, Julián
Santos, Cristina
Sanjuan, Xavier
Salazar, Ramón
Moreno, Victor
Piulats, Josep María
Sanz-Pamplona, Rebeca
Lung metastases share common immune features regardless of primary tumor origin
title Lung metastases share common immune features regardless of primary tumor origin
title_full Lung metastases share common immune features regardless of primary tumor origin
title_fullStr Lung metastases share common immune features regardless of primary tumor origin
title_full_unstemmed Lung metastases share common immune features regardless of primary tumor origin
title_short Lung metastases share common immune features regardless of primary tumor origin
title_sort lung metastases share common immune features regardless of primary tumor origin
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319789/
https://www.ncbi.nlm.nih.gov/pubmed/32591432
http://dx.doi.org/10.1136/jitc-2019-000491
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